Use of cadherin-11 antagonists to treat metabolic disorders and/or increase insulin sensitivity
Provided herein are methods and pharmaceutical compositions for the treatment of obesity-associated conditions using cadherin-11 antagonists.
1. A method for treating a subject having a metabolic disorder, comprising
administering to a subject having a metabolic disorder a cadherin-11 antagonist in an effective amount to improve glucose tolerance;
wherein the cadherin-11 antagonist is an anti-cadherin-11 antibody or an antigen-binding antibody fragment thereof;
wherein the subject is obese; and
wherein the metabolic disorder is selected from the group consisting of hepatic steatosis, type I diabetes, type II diabetes, hyperglycemia, metabolic syndrome, impaired insulin sensitivity, insulin resistance, impaired glucose tolerance, glucose intolerance, and non-alcoholic fatty liver disease (NAFLD).
2. The method of claim 1 , wherein the metabolic disorder is hepatic steatosis.
3. The method of claim 1 , wherein the metabolic disorder is non-alcoholic fatty liver disease (NAFLD).
4. The method of claim 1 , wherein the subject experiences a 2-5 fold reduction in blood glucose level or concentration and/or a 1-10% reduction in blood glucose level or concentration.
5. The method of claim 1 , wherein the metabolic disorder is treated independent of weight loss in the subject.
6. The method of claim 1 , wherein the cadherin-11 antagonist is an anti-cadherin-11 antibody.
7. The method of claim 1 , wherein the cadherin-11 antagonist is administered daily, weekly, biweekly, or monthly.
8. The method of claim 1 , wherein the cadherin-11 antagonist is administered orally or intravenously.
9. The method of claim 1 , further comprising administering to the subject a second therapeutic agent.
10. The method of claim 9 , wherein the second therapeutic agent is an anti-diabetic agent, anti-hyperglycemia agent, an anti-hypertension agent, an anti-hyperlipidemia agent, or an anti-obesity agent.
11. The method of claim 9 , wherein the cadherin-11 antagonist and the second therapeutic agent are administered simultaneously.
12. The method of claim 1 , wherein the metabolic disorder is type I diabetes.
13. The method of claim 1 , wherein the metabolic disorder is type II diabetes.
14. The method of claim 1 , wherein the metabolic disorder is hyperglycemia.
15. The method of claim 1 , wherein the metabolic disorder is metabolic syndrome.
16. The method of claim 1 , wherein the metabolic disorder is impaired insulin sensitivity.
17. The method of claim 1 , wherein the metabolic disorder is insulin resistance.
18. The method of claim 1 , wherein the metabolic disorder is impaired glucose tolerance.
19. The method of claim 1 , wherein the metabolic disorder is glucose intolerance.
20. A method for increasing insulin sensitivity index in a subject, comprising
administering to a subject having an abnormal insulin sensitivity index a cadherin-11 antagonist in an effective amount to increase the subject's insulin sensitivity index;
wherein the cadherin-11 antagonist is an anti-cadherin-11 antibody or an antigen-binding antibody fragment thereof; and
wherein the subject is obese.
21. The method of claim 20 , wherein the subject's insulin sensitivity index is increased by 0.0002 to 0.002 points or more.
22. A method for treating a subject having a metabolic disorder, comprising
administering to a subject having a metabolic disorder a cadherin-11 antagonist in an effective amount to reduce serum lipid level or concentration;
wherein the cadherin-11 antagonist is an anti-cadherin-11 antibody or an antigen-binding antibody fragment thereof;
wherein the subject is obese; and
wherein the metabolic disorder is a hyperlipidemia, hypercholesterolemia, or hypertriglyceridemia.
23. The method of claim 22 , wherein the metabolic disorder is hyperlipidemia.
24. The method of claim 22 , wherein the subject experiences a 2-5 fold reduction in serum triglycerides level or concentration and/or a 1-10% reduction in serum triglycerides level or concentration.
25. The method of claim 22 , wherein the metabolic disorder is hypercholesterolemia.
26. The method of claim 22 , wherein the metabolic disorder is hypertriglyceridemia.